A number of pharmaceutical compositions have a poor stability in an aqueous environment, which may reduce their shelf life to an unacceptable value. This is especially true for large molecules such as biological entities, especially antibody molecules and derived antigen binding molecules, recombinant factors, as well as for some small molecules such as antibiotics and steroid hormones. In some cases, it is possible to extend the shelf life by keeping the liquid composition in a cold environment.
Hence, it may be more advantageous in terms of stability, storage, and ease of shipping to prepare a solid form of the pharmaceutical composition, which may be reconstituted with a solvent shortly before its administration to a patient.
Solid forms of pharmaceutical compositions include powders, freeze-dried (or lyophilized) compositions, spray-dried, spray-freeze dried, vacuum dried or supercritical fluid dried compositions.
Solid forms are to be extemporaneously dissolved using an acceptable solvent composition to produce a solution for injection (so-called “reconstitution”).
The reconstitution steps may be carried out manually by the patient, a relative, a nurse or a healthcare professional, depending on the complexity of the reconstitution process.
Although such reconstitution may be straightforward and as short as a few seconds for some specific compositions, it may take up to tens of minutes to reconstitute some pharmaceutical compositions, which is considered as a long time. Long reconstitution times involving complicated series of steps often lead to lower compliance with said protocols, and so finally can result in administration of a wrong dose and even potentially affect the outcome of the treatment.
Another frequent problem is that some compositions are prone to the formation of foam, bubbles, gels or poorly wettable aggregates that require careful reconstitution and are thus considered “hard to reconstitute” per medical standards.
This is particularly the case for pharmaceutical compositions made of high concentrations of large molecules, such as viscous biological drugs such as but not limited to monoclonal antibodies, polyclonal antibodies, certain proteins or polypeptides. It is also the case when the reconstitution is made with less solvent volume than was originally taken out during processing towards a solid form, as it is frequently the case with formulations for injection so as to minimize the volume to be administered.
In any case the most conventional manual process for reconstitution of a solid form typically requires several steps to retrieve the solvent from a first container, inject it in a second container enclosing the solid form of the pharmaceutical composition, apply a given process to obtain a homogenous solution free of foam and/or dry aggregates, withdraw the reconstituted pharmaceutical from the second container for administration.
The reconstitution process requires that the operator pay a specific attention to each step, which is particularly tedious.
Besides, each of these above-mentioned steps themselves may require several object manipulations, including needles or spikes, thus implying a risk of personal injury and/or contamination in the case of a professional treating a patient.
At last, the quality of the reconstituted composition highly depends on the operator: if the steps are not carried out in a proper way, the composition obtained at the end of the reconstitution process may still contain trapped dry lumps or gel zones that can hardly be reached by the solvent and/or trapped air bubbles and/or foam, either in full volume or only limited to a ring at the air/liquid interface.
As a result, all of difficulties or problems abovementioned may result in the drug manufacturers to recommend the training of the user, or have the patient face less than expected medical benefit and/or poor compliance.